Metal-Responsive Fluorophore and Amikacin-Conjugated Heparin for Bacterial Cell Imaging and Antibacterial Applications.

The escalating prevalence of bacterial infections presents a formidable challenge to current global healthcare systems. Rapid identification and quantification of bacterial pathogens with anticipated sensitivity and selectivity are crucial for targeted therapeutic interventions to mitigate disease burden, drug resistance, and further transmission. Concurrently, there is a pressing need to innovate novel approaches to combat infections and counter antibiotic resistance.

Superhydrophobic Metal-Organic Framework-Based Composite Featuring Removal of Hydrophobic Drugs and Pesticides and Antibacterial Activities.

The widespread use and contamination of natural sources by new-generation drugs and pesticides have enhanced concern about environmental pollution. Understanding the above importance, we developed a superhydrophobic metal-organic framework (MOF) (: [ZrO(OH)(BDC-NH-CO-R)(BDC-NH)(CFCOO)]·2.5HO·4DMF) for ecological remediation via adsorption-based separation of hydrophobic drugs (flurbiprofen) and pesticides (fluazinam).

β-Carboline-based light and pH dual stimuli-responsive ion transporters induce cancer cell death.

Light and pH dual-responsive ion transporters offer better applicability for cancer due to higher tunability and low cytotoxicity. Herein, we demonstrate the development of pH-responsive β-carboline-based ionophores and photocleavable-linker appended β-carboline-based proionophores to facilitate the controlled transport of Cl across membranes, leading to apoptotic and autophagic cancer cell death.

A chloride-responsive molecular switch: driving ion transport and empowering antibacterial properties.

A molecular switch was developed to recognize and transport Cl across lipid bilayers. The XRD-crystal structure and NOESY NMR spectra of a potent 4-aminoquinazoline analogue confirmed Cl-induced conformation changes. Systematic biophysical studies revealed that the quinazoline moiety forms cooperative interactions of H and Cl ions with the thiourea moiety, resulting in the transport of H/Cl across the membranes.

Sulfonium-Cross-Linked Hyaluronic Acid-Based Self-Healing Hydrogel: Stimuli-Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic-Resistant Bacteria.

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment.

Imidazo[2,1-b]thiazole based indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor: Structure based design, synthesis, bio-evaluation and docking studies.

Indoleamine-2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme known to catalyse the initial and rate limiting step of kynurenine pathway of l-tryptophan metabolism. IDO1 enzyme over expression plays a crucial role in progression of cancer, malaria, multiple sclerosis and other life-threatening diseases. Several efforts over the last two decades have been invested by the researchers for the discovery of different IDO1 inhibitors and the plasticity of the IDO1 enzyme ligand binding pocket provide ample opportunities to develop new heterocyclic scaffolds targeting this enzyme.

Stimuli-responsive release of active anionophore from RGD-peptide-linked proanionophore.

Integrin-mediated cellular delivery was attempted to optimize practical applications of hydrophobic ionophores. The potent ionophore preferentially transports H/Cl across the lipid bilayers following a symport mechanism. The RGD-peptide-appended tag was stimulated by glutathione to generate the active ionophore, prompting the transport of Cl under the cellular environment.

Leishmania LPG interacts with LRR5/LRR6 of macrophage TLR4 for parasite invasion and impairs the macrophage functions.

Visceral leishmaniasis (VL) is a severe form of leishmaniasis, primarily affecting the poor in developing countries. Although several studies have highlighted the importance of toll-like receptors (TLRs) in the pathophysiology of leishmaniasis, the role of specific TLRs and their binding partners involved in Leishmania donovani uptake are still elusive. To investigate the mechanism of L.

Stimuli-responsive assembly and disassembly of anionic suprasomes with tunable antibacterial activity.

Host-guest complexation-based suprasomes successfully deliver benzimidazolium amphiphiles. β-CD and Zn or an acidic environment act as the stimuli for the assembly and disassembly of suprasomes. The supramolecular nanomedicine developed by encapsulating tetracycline showed strong and tunable antibacterial activity and holds potential for the next-generation vesicle-based drug delivery system.

Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity.

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn transport activities.

Transmembrane fluoride anion transport by -3,5-bis(trifluoromethyl)phenyl picket calix[4]pyrrole.

-3,5-bis(trifluoromethyl)phenyl picket calix[4]pyrrole 1 displays excellent fluoride anion transport activity across artificial lipid bilayers showing EC = 2.15 μM (at 450 s in EYPC vesicle) with high fluoride over chloride ion selectivity. The high fluoride selectivity of 1 was ascribed to the formation of a sandwich type π-anion-π interaction complex.

A small molecule potent IRAK4 inhibitor abrogates lipopolysaccharide-induced macrophage inflammation in-vitro and in-vivo.

Increasing evidence supports vanillin and its analogs as potent toll-like receptor signaling inhibitors that strongly attenuate inflammation, though, the underlying molecular mechanism remains elusive. Here, we report that vanillin inhibits lipopolysaccharide (LPS)-induced toll-like receptor 4 activation in macrophages by targeting the myeloid differentiation primary-response gene 88 (MyD88)-dependent pathway through direct interaction and suppression of interleukin-1 receptor-associated kinase 4 (IRAK4) activity. Moreover, incubation of vanillin in cells expressing constitutively active forms of different toll-like receptor 4 signaling molecules revealed that vanillin could only able to block the ligand-independent constitutively activated IRAK4/1 or its upstream molecules-associated NF-κB activation and NF-κB transactivation along with the expression of various proinflammatory cytokines.

Guanidine-Functionalized Fluorescent sp Carbon-Conjugated Covalent Organic Framework for Sensing and Capture of Pd(II) and Cr(VI) Ions.

Palladium is a key element in fuel cells, electronic industries, and organic catalysis. At the same time, chromium is essential in leather, electroplating, and metallurgical industries. However, their unpremeditated leakage into aquatic systems has caused human health and environmental apprehensions.

A photo-responsive fluorescent amphiphile for target-specific and image-guided drug delivery applications.

Multifunctional drug delivery systems are the centerpiece of effective chemotherapeutic strategies. Herein, we report the synthesis of an acetazolamide-linked cyanine-3-based NIR-responsive fluorescent macrocyclic amphiphile that self-assembled into spherical nanostructures in the aqueous medium a J-aggregation pattern. The amphiphile shows various favorable properties of lipids.

Stimuli-responsive transmembrane anion transport by AIE-active fluorescent probes.

Anticancer drug resistance implicates multifunctional mechanisms, and hypoxia is one of the key factors in therapeutic resistance. Hypoxia-specific therapy is considered an extremely effective strategy to fight against cancer. The development of small molecule-based synthetic anion transporters has also recently drawn attention for their potential therapeutic applications against several ion-transport-associated diseases, such as cancer and others.

Sulfonium-based liposome-encapsulated antibiotics deliver a synergistic antibacterial activity.

The devastating antibacterial infections, coupled with their antibiotic resistance abilities, emphasize the need for effective antibacterial therapeutics. In this prospect, liposomal delivery systems have been employed in improving the efficacy of the antibacterial agents. The liposome-based antibiotics enhance the therapeutic potential of the new or existing antibiotics and reduce their adverse effects.

Photoresponsive transformation from spherical to nanotubular assemblies: anticancer drug delivery using macrocyclic cationic gemini amphiphiles.

We developed NIR-light-responsive macrocyclic cationic gemini amphiphiles, one of which displayed various favorable properties of lipids. The NIR-light-mediated cleavage of the strained dioxacycloundecine ring led to the conversion of the spherical to a nanotubular self-assembly in the aqueous medium. This photo-mediated transformation from the spherical to nanotubular self-assembly resulted in the release of encapsulated hydrophobic anticancer drug molecule doxorubicin (Dox) in a controlled manner.

Inhibition of immunosuppressive indoleamine 2,3-dioxygenase by targeting the heme and apo-form.

Inhibition of immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is considered one of the potential approaches in the fight against cancer and other diseases. Comprehensive biophysical and cellular studies have shown that quinine derivatives effectively inhibit the activity of IDO1. Mechanistic studies revealed that the potent quinine derivatives compete with heme for binding to apo-IDO1 and perturb its reversible binding propensity to apo-IDO1 via the formation of a heme-inhibitor complex.

Multi-stimuli controlled release of a transmembrane chloride ion carrier from a sulfonium-linked procarrier.

In recent times, anion transporters have received substantial consideration due to their ability to disrupt the ionic equilibrium across membrane bilayers. While numerous Cl- ion transporters were developed for channelopathies, unfortunately, poor aqueous solubility precluded their bioapplicability. Herein, we demonstrate the development of a multi-stimuli activatable anion transport approach to induce regulated transport of Cl- ions across membranes under specific conditions.

Biological applications of synthetic anion transporters.

The use of synthetic ion transporters for alteration of the concentration of ions across cell membranes has drawn attention from scientists over the last two decades. This ion transport property has been sensibly used to reduce the viability of cancer cells mainly due to the disruption of their ion homeostasis, leading to the perturbation of their abnormal pH gradient. The use of the proanionophore strategy has been recently adopted to increase cellular deliverability and reduce unwanted cytotoxicity towards normal cells.

Transforming growth factor beta orchestrates PD-L1 enrichment in tumor-derived exosomes and mediates CD8 T-cell dysfunction regulating early phosphorylation of TCR signalome in breast cancer.

Tumor cells promote immune evasion through upregulation of programmed death-ligand 1 (PD-L1) that binds with programmed cell death protein 1 (PD1) on cytotoxic T cells and promote dysfunction. Though therapeutic efficacy of anti-PD1 antibody has remarkable effects on different type of cancers it is less effective in breast cancer (BC). Hence, more details understanding of PD-L1-mediated immune evasion is necessary.

Quinine-Based Semisynthetic Ion Transporters with Potential Antiproliferative Activities.

Synthetic ion transporters have attracted tremendous attention for their therapeutic potential against various ion-transport-related diseases, including cancer. Inspired by the structure and biological activities of natural products, we synthesized a small series of squaramide and thiourea derivatives of quinine and investigated their ion transport activities. The involvement of a quinuclidine moiety for the cooperative interactions of Cl and H ions with the thiourea or squaramide moiety resulted in an effectual transport of these ions across membranes.

Chloride Ion Transport by PITENINs across the Phospholipid Bilayers of Vesicles and Cells.

Small-molecule-based Cl ion carriers are gaining revived attention because of their recently discovered role toward anticancer activity. Herein, we showed that the anticancer agents, PITENINs, have an efficient transmembrane Cl ion transport activity. Theoretical calculations, H NMR titration, and spectrophotometric analysis suggest that the PITENINs strongly bind with a Cl ion.

A stimuli-responsive anticancer drug delivery system with inherent antibacterial activities.

We describe a novel class of stimuli-sensitive sulfonium-based synthetic lipids, which exhibit several favorable biophysical properties of phospholipids. The potent sulfonium-based lipid was successfully disassembled by glutathione to release the encapsulated drug molecules in a controlled manner. The cationic lipid also showed lower cytotoxicity against mammalian cells and displayed moderate antibacterial activities.